This invention is generally in the field of medical devices, and more particularly relates to implantable drug delivery devices for controlled release of drug locally to a tissue site.
The efficacy of many drugs is directly related to the way in which they are administered. Various systemic methods of drug delivery include oral, intravenous, intramuscular, and transdermal. These systemic methods may produce undesirable side effects and may result in the metabolization of the drug by physiological processes, ultimately reducing the quantity of drug to reach the desired site. Accordingly, a variety of devices and methods have been proposed to deliver drug in a more targeted manner, such as locally, to address many of the problems associated with systemic drug delivery.
Prostatitis is an inflammatory condition of the prostate gland. Typically, prostatitis is a painful disorder that presents with symptoms that often include chronic pelvic pain, urinary dysfunction (in the form of frequency, urgency or weak stream, pain on urination) and sexual dysfunction. The condition is estimated to be prevalent among 10% of all men and is believed to be symptomatic in half the male population at some point in their lifetime. Prostatitis can occur either as an acute infection of the prostate gland, known as acute bacterial prostatitis, or more commonly as a recurring condition, known as chronic prostatitis.
Chronic prostatitis is characterized as being bacterial (CBP) or abacterial (ACP) based on the isolation of a suspected causative pathogen from the prostatic fluid or urine. Bacteria are believed to cause a significant percentage of chronic prostatitis cases, such as 5 to 15% of such cases. Current recommendations provide that all patients presenting with chronic prostatitis (both CBP and ACP) should be treated initially with antibiotics for 2 weeks and should receive continued treatment if symptoms improve. The choice of antibiotic can be critical, as the prostate and nearby seminal vesicles present a significant pH gradient. Thus, the chosen antibiotic should have sufficient chemical stability over a range of pH (e.g., 7.2 to 8.0) while also exhibiting effective penetration into the prostate gland. The zwitterionic fluoroquinolones such as ciprofloxacin (CIP) and levofloxacin have surpassed older drug treatments for chronic prostatitis such as trimethoprin-sulfamethoxazole (TMP-SMZ) in both effective bacterial eradication and cost-effectiveness. A 500 mg dose of CIP administered twice a day for 28 days yielded bacteriological cure rates of 63-76% in clinical studies, whereas most studies on TMP-SMZ or TMP alone yielded efficacy rates between 30-50% and required longer duration of therapy, such as 90 days. Significant room therefore still exists for improvement in the cure rate.
Some have advocated direct injection of antibiotics to the prostate gland due to the relatively high failure rate of systemic antibiotic administration. The failure of oral antibiotics is mainly thought to be due to an associated local autoimmune disease process and the possible presence of intraprostatic bacterial biofilms which resist drug penetration, providing a therapeutic argument for local antibiotic administration. Guercini et al. (Arch Ital Urol Androl 77:87-92 (2005)) have also demonstrated enhanced improvement in therapy with additional co-administration of betamethasone, an immuno-suppressing steroid infused in a cocktail solution with antibiotics, to the prostate in order to counter the effects of the autoimmune disease process. In that study, chronic prostatitis patients who had experienced repeated failure of oral antibiotics in the previous 12 months underwent prostatic infiltration of antibiotics and betamethasone. In the study, 68% of the study participants were effectively cured, and 13% of the participants showed no response. While local prostate antibiotic injection has shown reasonable efficacy in clinical trials, it has not yet become a popular or widespread therapy in use among most urologists.
The seminal vesicles are a pair of coiled tubular glands which form lateral outpouchings of the ampulla of the vas deferens, which connects the epididymis of the testes to the prostate gland. The seminal vesicles and the ampulla form the ejaculatory duct which empties into the prostate gland. Infection and inflammation of the seminal vesicles (vesiculitis) is uncommon in the United States, and it is usually treated with systemic antibiotics. Cancer originating in the seminal vesicles is rare, although secondary invasion of tumors from the nearby prostate gland, bladder, or rectum is more common. One identified brachytherapy treatment for prostate cancer with secondary seminal vesicle involvement includes the implantation of radioactive 103Pd seeds.
Accordingly, a need exists to provide a local drug delivery device and method to replace multiple intraprostatic injections as a sustained treatment of antibiotics over an extended period. In addition, it would be desirable to provide alternatives for treating vesiculitis, cancer, or other diseases and conditions involving the seminal vesicles, ampulla, prostate, and/or surrounding tissues, particularly in a minimally invasive manner for local delivery of one or more drugs.
It would be further desirable to provide treatments in which a therapeutically effective amount of drug can be administered over an extended period to one or more urological tissue sites without a strict or complicated dosing regimen. In addition, there is a need for controlled drug device that is suitable for delivery into and retention in a genitourinary site in a patient, such as a seminal vesicle, vas deferens, ejaculatory duct, or prostate. In particular, there is a need for materials of construction that are functional for storing and releasing drug, that are suitably elastic for minimally invasive deployment and retention, and that do not require explantation following completion of the drug release.